introduction to clinical sciences Flashcards
Define inflammation
The body’s response to injury or infection using different types of cells
How can inflammation be sub divided?
Acute/ neutrophil mediated or chronic/macrophage/ lymphocyte mediated
what type of cell are neutrophil polymorphs?
WBC
where are neutrophil polymorphs made?
Bone marrow
what is the lifespan of neutrophil polymorphs?
2-3 days
what gives neutrophil polymorphs their name?
their multi lobar nucleus
which organelle allows neutrophil polymorphs to carry out their functions?
lysosomes allow them to phagocytose bacteria
which cells are the first to arrive at the site of infections?
neutrophil polymorphs
where do neutrophil polymorphs die?
at the site of infection
what type of cell is a macrophage?
WBC
How long do macrophages live for ?
months to years
what are the functions of macrophages?
phagocytose bacteria, transport material to lymph nodes, presenting it to lymphocytes and triggering a secondary immune response
How long do lymphocytes live for ?
years
what do lymphocytes produce?
inflammatory mediators and antibodies
which cells provide immunological memory?
lymphocytes
Which cells produce collagenous connective tissue?
fibroblasts
Describe the sequence of acute inflammation
- Injury or infection
- neutrophils arrive and phagocytose and release enzymes
- macrophages arrive and phagocytose
4.either resolution or progression to chronic inflammation
Give 3 examples of acute inflammation
- acute appendicitis
- frostbite
- streptococcal sore throat
describe the sequence of chronic inflammation
- either progresses from acute inflammation or begins as chronic inflammation
- no or very few neutrophils
- macrophages, lymphocytes and fibroblasts
- can resolve if theirs no tissue damage but often ends up as repair and formation of scar tissue
Give an example of an illness that begins as chronic inflammation
infectious mononucleosis
What is a granuloma
type of inflammation where collections of macrophages/ histocytes are surrounded by lymphocytes
when may granulomas be significant?
when they may be due to a myobacterial infection such as TB or leprosy
what other disease may granulomas be seen in ?
Crohn’s disease
when does acute inflammation occur
to initial tissue injury
Describe the onset and duration of acute inflammation
early onset, short duration
Which cells are involved in acute inflammation
monocytes and neutrophils
In 3 steps describe acute inflammation
- Vascular component, dilation of vessel and increased permeability
2.exudative component, leakage of protein rich fluid - neutrophil polymorph, recruited to tissue (cellular exudate)
Describe the 4 steps of neutrophil polymorph recruitment
- migration- increased plasma viscosity and slowing of flow causes neutrophils to migrate to plasmatic zone
- adhesion- neutrophil pavementing to endothelium in venules
3.emigration- neutrophils pass through endothelial cells, basal lamina and vessel wall
4 diapedesis- RBC’s may also escape from vessel, which is passive transport
Give 6 causes of acute inflammation
- microbial infections- bacteria and parasites
- hypersensitivity reactions - parasites
- physical agents- trauma, heat or cold
- chemicals - corrosives and acid
5.bacterial toxins - tissue necrosis- ischaemic infarction
How may acute infection appear?
- rubor, due to dilation of vessels
2.calor, heat peripherally
3,tumor, swelling due to oedema or mass - dolor - pain
loss of function
Describe the macroscopic appearance of chronic inflammation
- chronic ulcer
- chronic abscess
3.granulomatous inflammation - fibrosis
Describe the microscopic appearance of chronic inflammation
lymphocytes, plasma cells and macrophages, continuing destruction of tissue, no exudation
what can the presence of granulomas and eosinophils suggest?
parasite
what are 3 causes of primary chronic inflammation?
- resistance of infective agent,
2, endogenous/ exogenous materials - autoimmune disease
Name a cell derived inflammatory mediator
histamine
How does repair happen after inflammation?
fibroblasts are stimulated by cytokines to proliferate and increase collagen synthesis
what do granulocytes release?
prostoglandins
what do prostoglandins cause ?
fever and pain
describe 1st intention healing
bringing skin together via surgery, fribrin and then collagen join edges
describe 2nd intention healing
New cells filling in gap
Describe repair
tissues that cant regenerate are replaces by fibrous tissue
name 6 cells that can regenerate
hepatocytes, pneumocytes, all blood cells, gut epithelium, skin epithelium, osteocytes
Name 2 cells that cant regenerate
myocardial cells, neurones
which model demonstrates the causes of thrombosis?
Virchow’s triad, 2 of these are required for thrombosis to happen
Define thrombosis
solidification of blood contents that forms within the intact vascular system during life
What are the 3 elements of virchow’s triad
1.hypercoagulability
2.stasis of blood
3.vessel wall injury
How is normal blood flow described?
laminar
how is interrupted blood flow described
turbulent
How does damage to the endothelium trigger thrombus formation?
collagen is revealed, this attracts platelets, platelet aggregation begins thrombus formation, fibrin is deposited
How can slow blood flow lead to thrombus formation?
causes endothelium nitrous oxide production to reduce, which can lead to deep vein thrombosis
which drug inhibits platelet aggregation?
aspirin
How may arterial thrombi appear?
cold, painful, pulseless, pale, possible gangrene
what commonly causes arterial thrombi?
atheroma
what can arterial thrombi result in?
Myocardial infarction, stroke or gnagrene
How may venous thrombi appear?
tender, red, swollen
what commonly causes venous thrombi?
stasis across valves
what can venous thrombi lead to?
deep vein thrombosis or pulmonary embolisms
what are the 4 fates of thrombi?
- resolved
- organised (scar formation)
3.recanalisation( capillaries grow) - embolus
define emboli
mass of material in vascular system able to lodge in a vessel and block its lumen
where do arterial emboli lodge
heart, brain or peripheries
where do venous emboli lodge?
pulmonary arteries
what determines the impact of a venous embolus?
it’s size
Define ischaemia
reduction in blood flow to a tissue caused by constriction or blockage of the vessels supplying it
define infarction
death of the tissue due to severe or prolonged ischaemia
which organs have a dual supply?
Liver, brain, lungs
what impact does dual supply have on infarction?
it makes organs less susceptible to infarction
how are non dual supply organs described?
end artery supplied
define reperfusion injury
damage to tissue during reoxygenation
Describe the steps in atherogenesis
- Damage to endothelial cells
- endothelium secretes chemoattractants
- leukocytes migrate and accumulate in intima
4.foam cells/ macrophages/ T-lymphocytes form fatty streaks
5.foam cells rupture, releasing lipids - smooth muscle cells migrate from media to intima
- dense fibrous cap with necrotic core is formed
How can atheroma lead to ischaemia?
partially occluding the lumen of a vessel
How can an atheroma lead to an infarction?
The plaque can rupture, forming a thrombus, fully occluding the lumen
Which arteries does atherogenesis affect the most?
LAD, circumflex and RCA
What are the risk factors for atherogenesis?
- Age
- smoking
- obesity, high serum cholesterol
4.poorly controlled diabetes
5.hypertension
6.family history - being male
what causes cardiac myocyte damage?
insufficient oxygen rich blood, increased myocardial workload, coronary artery occlusion, atheroma, valvular disease, anaemia
In ascending order of severity describe cardiac monocyte damage problems
stable angina, unstable angina, NSTEMI and STEMI
where do atheromas form
high pressure arteries, usually not pulmonary
define apoptosis
genetically programmed removal of small groups/ individual cells without release of harmful products to surrounding cells
what is apoptosis important for ?
normal physiology
what DNA damage may result in apoptosis of a cells?
- single strand break
- double strand break
3.cross linkage - base alteration
How does a cell apoptose?
it’s an activated caspase enzyme cascade
which protein triggers apoptosis?
p53, it can detect enzyme damage
Define necrosis
unprogrammed cell death due to an adverse event
what follows necrosis?
acute inflammation
what are the different types of necrosis?
coagulative, liquefactive, caseous, gangrenous, fat, fibrinoid
How does necrosis damage cells
mitochondria releases ROS
when may you see caseous necrosis?
In TB, it has a soft cheese texture
Define congenital disease
present at birth, not always inherited but usually environmental
define inherited disease
caused by an inherited genetic abnormality
describe acquired disease
caused by non genetic factors
which cells do autosomal inheritance affect
somatic cells rather than sex cells
define polygenic inheritance
where many genes contribute to disease
when do genetic diseases manifest?
they may present later in life
define hypertrophy
increase size of tissue caused by an increase in size of constituent cells
define hyperplasia
increase in size of tissue due to an increase in the number of constituent cells
define atrophy
decrease in size of tissue due to a decrease in number of cells or their size
define metaplasia
change in differentiation from a fully differentiated cell to another fully differentiated cell
define dysplasia
morphological changes seen in cells in their progression towards being cancer
when may you see hypertrophy and hyperplasia in a tissue?
in the uterus during pregnancy
when may you see atrophy
dementia
what is the heyflick limit?
The number of times a cell can divide
what determines the heyflick limit
the telomeres shorten with each division, they eventually get so short that they can’t divide
what causes dermal elastosis?
UV B light causes cross linking of collagen, which causes clumping
what causes osteoporosis?
increased bone resorption, decreased bon formation and lack of oestrogen
what causes cataracts
UV B light cross linking proteins in the lense
what causes senile dementia?
plaques and neurofibrillary tangles
what causes sarcopenia?
decreased growth hormone, decreased testosterone, increased catabolic cytokines
what causes deafness?
loss of hair in cochlear, hair cells cant divide and they’re damaged by noise
what is the only definitive method for reducing aging ?
calorie deficit, metabolites damage cells so reducing the metabolites reduces damage
where do basal cell carcinomas invade and how can we treat them?
They only invade locally, so complete excision is a cure
List the systemic symptoms of leukaemia
- weight loss
- fever
3.frequent infections
what is the muscular symptom of leukaemia?
weakness
what are the bone and joint symptoms of leukaemia?
pain or tenderness
what are the psychological symptoms of leukaemia?
fatigue and weakness
How may the spleen or liver look when someone has leukaemia?
enlarged
how may the lymph nodes appear in someone with leukaemia?
swollen
what respiratory problem would someone with leukaemia experience?
shortness of breath
what symptoms of leukaemia appear on the skin
- night sweats
- easy bleeding and bruising
3.purplish patches or spots
where do carcinomas spread
to the lymph nodes that drain the site of carcinoma
which carcinomas are commonly spread to the bone?
breast, prostate, lung, kidney, thyroid
Describe the breast cancer treatment plan
confirm the patient has breast cancer
1. has it spread to the axilla?
yes- axillary node clearance
no- has it spread to the rest of the body?
yes- chemo
no- surgery with or without axillary lymph node clearance
what may be present after a tumour is completely exercised?
micro metastases
define adjuvant therapy
extra treatment given after surgical excision, ie radiotherapy after a lumpectomy or anti- oestrogen if breast cancer is oestrogen receptor positive
define carcinogenesis
the transformation of normal cells into neoplastic cells through permanent genetic alterations or mutations
what does carcinogenesis apply to ?
malignant neoplasms
what does oncogenesis apply to?
malignant and benign tumours
define carcinogens
agents known or suspected to cause tumour
what are the differences between carcinogenic and oncogenic?
carcinogenic is cancer causing and oncogenic is tumour causing
what percentage of cancer risk is environmental factors?
85%
name 3 issues with identifying carcinogens
- latent periods can last decades
- complexity of environment
- ethical constraints
Give an example of epidemiological evidence of carcinogens
hepatocellular carcinoma is common in areas with high hepatitis B/C and mycotoxins
Give an occupational carcinogenic risk
bladder cancer has a high incidence in aniline dye and rubber industries due to beta naphythylamine
Give a behavioural carcinogenic risk
smoking and lung cancer
Give an example of direct evidence of carcinogens
radioactive iodine isotopes released into atmosphere by chernrobyl nuclear reactor 1986, in 1990 there was increased incidence of thyroid cancer in ukranian children
describe chemical carcinogens
some act directly, however most require conversion from pro-carcinogens to ultimate carcinogens, required enzyme may be ubiquitous or confined to certain organs
Describe viral carcinogens
cause 10-15% of all cancers
Give examples of DNA viral carcinogens
1.human herpes virus- kaposi sarcoma
2.epstein Barr virus- Burkitt lymphoma( nasopharyngeal carcinoma)
3.hepatitis B- hepatocellular carcinoma
4. human papillomavirus- squamous cell carcinomas of the cervix, penis, anus, head and neck
4. merkell cell polomavirus- merkell cell carcinoma
Give examples of RNA viral carcinogens
- human T-lymphocytic virus- adult T-lymphocyte leukaemia
- Hepatitis C virus- hepatocellular carcinoma
give an effect of ionising radiation
skin cancer in radiographers
give an effect of non ionising radiation
lung cancer in uranium minors
what does UVA/B increase the risk of?
Basal cell carcinoma, melanoma or squamous cell carcinoma
what is xerdoma pigmentosum?
a hereditary condition that is characterised by extreme sun sensibility, high risk of cancer and other medical issues
what does an increase in oestrogen cause?
An increase in mammary/ endometrial cancer
what does an increase in anabolic steroids cause?
an increase in hepatocellular carcinoma
which mycotoxin causes hepatocellular carcinoma?
aflatoxin B
Give 2 examples of parasites causing cancer
- Clonorchis synesis causes cholangiocarcinoma
- Schistosoma causes bladder cancer
Give examples of 2 miscellaneous carcinogens
- asbestos
- metals
Give 2 examples of host factors affecting risk of developing cancer
- In India and SE Asia there are increased rates of oral cancer due to betal chewing
- Skin cancer is lower in darker skinned people
Give 2 examples of inherited predisposition to developing cancer
- familial polyposis coli
2.retinoblastoma
what effect does age have on cancer risk?
it increases with age, due to the incidence of genetic mutations being acquired through life
How does alcohol usage affect the risk of cancer
increases the risk of mouth, oesophagus, liver, colon, breast and kidney cancer
How does exercise affect the risk of cancer
reduces risk of colon and breast cancer
How does unprotected sex affect thee risk of cancer?
increased risk of HPV related cancers
what is a premalignant lesion?
An identifiable local abnormality associated with increased risk of malignancy at that site
Give 4 examples of premalignancy lesions
- colonic polyps
- cervical dysplasia
3.ulcerative colitis - undescended testes
Give 1 example of transplacental exposure causing an increased risk of cancer.
diethylstilboestrol, causes increased risk of vaginal cancer
Define neoplasia
A lesion resulting from autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
describe the 2 spectrums that neoplasia is on
1.malignant to benign
2. fatal to subclinical
which 2 things make up neoplasia?
- neoplastic cells and stroma
describe neoplastic cells
derived from nucleated cells, usually monoclonal, growth pattern related to parent cells, synthetic activity related to parent cells
describe stroma
connective tissue framework, mechanical support and nutrition
what is tumour angiogenesis?
when a tumour reaches larger than 2mm in size it has to become vascularised to survive
what are the 2 methods of classifying tumours?
1.behavioural, benign, borderline or malignant
2.histogenetic, cell of origin
Describe benign neoplasms
localised, non invasive, slow growth, low mitotic activity, closes resemblance to normal tissue, circumscribed or encapsulated, nuclear morphometry often normal, necrosis is rare, ulceration is rare, grow on mucosal surfaces, often exophytic ( grow up and out)
why are benign tumours problematic?
- they put pressure on adjacent structures
- obstruct flow
- produce hormones
- transformation into malignant neoplasms
- anxiety
Describe malignant neoplasms
invasive, metastases, rapid growth rate, variable resemblance to normal tissue, poorly defined or irregular border
Who is the best snack?
You.
Describe the cellular properties of malignant neoplasms
Hyperchromatic nuclei, pleomorphic nuclei, increased mitotic activity, necrosis is common, ulceration is common, grow on skin and mucosal surfaces, often have endophytic growth
Why do malignant neoplasms cause problems?
- destruction of adjacent tissues
- metastases
- blood loss from ulcers
- obstruction of flow
- hormone production
- paraneoplastic effects
- anxiety and pain
How are malignant neoplasms circumscribed?
Poorly
where may neoplasms arise from?
epithelial cells, connective tissue, lymphoid, haematopoietic organs
What is the suffix for most neoplasms
‘-oma’
Describe 2 benign epithelial neoplasm prefixes
1.papilloma, benign tumour of non glandular non secretory epithelium ie squamous cell papilloma
2. Adenoma, benign tumour of glandular or secretory epithelium, ie colonic adenoma
describe the prefix for malignant epithelial neoplasms
carcinoma, malignant tumour of epithelial cells ie urothelial carcinoma
How do you describe a malignant neoplasm of glandular epithelium
adenocarcinoma
Give 4 examples of benign connective tissue neoplasms (normal names)
- Lipoma
- Chondroma- cartilage
- Osteoma- bone
- Angioma- vascular
Give 3 examples of benign connective tissue neoplasms (abnormal names)
- Rhabdomyoma - striated muscle
- Leiomyoma, smooth muscle
- Neuroma, nerves
What are malignant neoplasms of the connective tissue prefixed with?
sarcoma
when the cell type of origin is unknown what is a tumour called?
anaplastic
give the exceptions as to which ‘-om’as’ are not neoplasms
granulomas, mycetoma, tuberculoma
Give 3 examples of malignant neoplasms that aren’t carcinoma or sarcoma
1.melanoma, malignant neoplasms of melanocytes
2. mesothelioma, malignant neoplasm of mesothelial cells
3. lymphoma, malignant neoplasm of lymphoid cells
Give 4 examples of eponymously named tumours
- Burkitt’s lymphoma
- Ewing’s sarcoma
- Grawitz tumour
- Kaposi sarcoma
which cell do all immune cells develop from?
A multipotential hematopoietic stem cell called a hemocytoblast
What 2 cell types does a hemocytoblast differentiate into?
a common myeloid progenitor or a common lymphoid progenitor
Describe the different cells that derive from a common myeloid progenitor
- megakyocyte
- erythrocyte
- mast cell
- myeloblast
which cells doe thrombocytes arise from?
megakaryocytes
which cells arise from a myeloblast?
- basophils
- neutrophil
- eosinophil
- monocyte
which cell does a macrophage arise from?
A monocyte
which cells arise from common lymphoid progenitors
- natural killer cells or small lymphocytes
which cells does a small lymphocyte give rise to?
T lymphocytes or B lymphocytes
which cells do plasma cells arise from?
B cells
where doe all immune cells originate?
Bone marrow
where do T cells mature?
thymus
where do B and T cells accumulate?
Lymph nodes
where are red blood cells removed?
The spleen
what can cause splenomegaly (enlarged spleen)?
Leukaemias
Describe the innate immune system
non- specific defence system you were born with, an example is mucus or inflammation
describe adaptive immunity
acquired defence system to destroy/ prevent growth of pathogens , ie antibodies
how fast is the adaptive immune system compared to the innate system?
slow, it takes days to weeks whereas the innate is fast, hours to days
describe the regulation in the innate and adaptive system
positive and negative in innate and just positive in adaptive
describe the amplification in the innate and adaptive immune response
an insignificant amount in the innate and a lot in the adaptive
